Neoplasma Vol.52, p.126-136, 2005
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Title: Peroxisome proliferator-activated receptors (PPAR) agonists affect
cell viability, apoptosis and expression of cell cycle related
proteins in cell lines of glial brain tumors
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Author: N., STRAKOVA
; J., EHRMANN
; J., BARTOS
; J., MALIKOVA
; J., DOLEZEL
; Z., KOLAR
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Abstract: The nuclear receptors PPARs (peroxisome proliferator-activated
receptors) are transcription factors activated by specific
ligands. PPARs play an important role in carcinogenesis,
inflammation, atherosclerosis, lipid metabolism and diabetes.
There is evidence that activation of PPARs by specific ligands is
able to suppress the growth of different types of human cancer by
mechanisms including the growth arrest, apoptosis and induction of
differentiation, although the detailed signalling pathways have
not been completely elucidated to date. The aim of our study was
to determine whether synthetic ligands of PPARa and PPARg could
affect the viability, proliferation, differentiation, apoptosis
and expression of some cell cycle related proteins in glial tumor
cell lines. The study was performed on human glioblastoma cell
lines U-87 MG, T98G, A172 and U-118 MG. Cell lines were treated by
ligands of PPARa (bezafibrate, gemfibrozil) and PPARg
(ciglitazone). MTT, flow cytometry, TUNEL assay and immunoblotting
were used for detection of changes in cell viability,
proliferation, differentiation and apoptosis. Bezafibrate,
ciglitazone and gemfibrozil inhibited viability of glioblastoma
cell lines. The synthetic ligands significantly reduced or induced
the expression of cyclins, p27Kip1, p21Waf1/Cip1, MDM-2, Bcl-2,
Bax, PARP, Caspase 3, androgen receptors, etc. and did not affect
the expression of the differentiation marker GFAP. Flow cytometry
confirmed arrest of the cell cycle although the detection of
apoptosis was controversial. Apart from hypolipidemic and
hypoglycaemic effects, PPAR ligands may also have significant
cytostatic effects of potential use in anticancer treatment.
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Keywords: PPAR, glioblastoma, cell cycle, apoptosis, fibrates,
thiazolidinediones
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Year: 2005, Volume: 52, Issue: |
Page From: 126, Page To: 136 |
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